Building a ‘better' brain

Do an Internet search for "memory boosters," "smart pills" or "cognitive enhancers" and you will get 2 million to 3 million hits. "Ginseng" or "ginkgo biloba" yield more than 50 million hits, each linking to pages offering products to improve memory. At the supermarket, dozens of products touted as "brain boosters" are offered for modest prices. Cognitive enhancement is now a billion-dollar industry.

The belief that various herbs and potions improve memory and cognitive functioning dates back to antiquity. But it wasn't until the mid-20th century that scientists, drawing on new models and techniques, began to make serious progress toward unlocking the mystery of memory.

In 1968, surveying the burgeoning literature in the field, University of California, Berkeley, experimental psychologist David Krech, PhD, optimistically claimed that by the 21st century, educators and parents might very well have a new "psychoneurobiochemopharmacopia" of elixirs that would improve learning, memory and perhaps even intelligence. However, the ethical concerns of such treatments tempered Krech's optimism.

What fueled Krech's optimism and wariness?

Before 1955, one would be hard-pressed to find labs dealing with the relationships among the brain, biochemistry and behavior. One exception was the enriched environment research initiated in 1951 by Krech and his colleagues at Berkeley that, in some form, continues in other labs today.

These early experiments sought to uncover what, if any, changes in brain structure and function occurred when a dozen rats were reared together in an environment packed with toys and opportunities for exploration and problem-solving. They found that these rats, compared with their identical twins isolated in cages and devoid of playmates and stimulating materials, had significantly heavier and deeper cortices and much more neurochemical activity.

Creating even more of a stir was a second and parallel research track appearing in the late 1950s centered on the role of ribonucleic acid (RNA) in learning and memory processes. Neurobiologist Holger Hyden of the University of Goteborg reported that rats trained to balance on a wire and complete other tasks had an increase in a slightly altered form of RNA in their brains — that, in effect, the synthesis of RNA accompanied learning. Keenly aware of both the basic and applied importance of this work, researchers at universities and pharmaceutical companies immediately set out to devise experiments to see if the manipulation of RNA synthesis during training — its inhibition and its acceleration — would affect the acquisition of memories.

The early 1960s were ripe for such investigations. Hot on the heels of Watson and Crick's pioneering work on the structure and function of DNA, researchers turned their attention to the physiological and biochemical aspects of learning and memory. If DNA "coded" for ancestral information, might RNA be a parallel code for acquired information? Each year the National Institutes of Health and the National Science Foundation awarded grants, interdisciplinary conferences were held and researchers published dozens of experimental reports. Newspaper headlines heralded impending breakthroughs in the treatment of — perhaps even cures for — dementia and various other cognitive disabilities.

A watershed event occurred in 1965 when Krech arranged a multi-session symposium on "Brain, Biochemistry and Behavior" at the American Association for the Advancement of Science meeting. Approximately 2,000 attendees heard prominent geneticists, anatomists, biochemists, physiologists, pharmacologists, neurologists and psychologists who discussed the tantalizing evidence on the role of RNA. Biochemist Bernard Agranoff of the University of Michigan reported that administering various RNA or protein-synthesis inhibitors before or just after training had significant adverse effects on the retention of newly acquired learning in goldfish. In other experiments, James McGaugh and Lewis Petrinovich (both former students of Krech) demonstrated that increasing RNA synthesis by administering strychnine improved learning. Psychiatrist Ewen Cameron of McGill University reported that yeast RNA administered to elderly people suffering from dementia had a positive effect on their memory. Researchers at Abbott Labs reported that Cylert (magnesium pemoline) enhanced learning in rats and, more important, that human trials were planned.

In both his introductory remarks and closing commentary at the symposium, Krech worried out loud. The potential benefits of this research, he agreed, were enormous. But the social and ethical questions raised by this work were of the same magnitude as those resulting from the achievements of the atomic physicists: If the biochemical tools are developed, will governments be tempted to manipulate the behavior of their citizens? Should scientists or governments tamper with individuals' natural endowments? Should such potions, once developed, be used only to treat cognitive deficiencies or should they be used to enhance normal functioning? Who gets what and when? Who bears the cost of these treatments? Who decides? Who keeps watch over those who do?

Krech's comments quickly spread through the mass media. On the last day of the symposium a New York Times headline proclaimed "Mind Control on Way, Scientist Warns." This was followed the next day by a Times editorial, "Controlling the Mind," which lauded Krech's position and called for "free men in democratic societies to grapple with the problems of advances in science and to find ways to control the results."

This was not the first time Krech delved into the relationship between the scientific and broader social worlds. A founding member of Div. 9 (Society for the Psychological Study of Social Issues) in 1936, Krech fervently believed that psychology could — and should — contribute to a better understanding of social problems and that its results might improve the quality of life for all. Social responsibility was a matter for everyone, he believed; neither policymakers nor scientists should act alone.

Over the next several years, Krech relentlessly drew attention to the latest research results and the ethical questions that in his view demanded the attention of citizens, scientists and politicians alike. His article, "Controlling the Mind Controllers," published shortly after the AAAS symposium, set the stage. He appeared as a panelist on the television special "Frontiers of the Mind" and on the radio broadcast "Mastering the Mind." He debated the issues with Nobel laureate biologists Joshua Lederberg and Sir Peter Medawar. He brought the issues to the attention of educators at talks sponsored by the U.S. Office of Education and the Charles Kettering Foundation. And he took his message to Washington when, in April 1968, he appeared before Walter Mondale's Senate subcommittee conducting hearings to consider the creation of a Commission on Health Science and Society. There, Krech insisted that a hasty patchwork policy would not do. Neither the scientist nor the politician should be the final arbiter — an informed collaborative effort was needed.

Although Mondale's proposed commission failed to garner the necessary votes, Krech soldiered on. His last major talk before he died, an invited address at APA's 84th Annual Convention in 1976, was titled "Prospects for Control."

Today, the issues Krech raised are still very much alive. Indeed, they are more pronounced. Over the past four decades, research on various agents to improve cognitive performance has broadened and accelerated. Given the focus on attention-deficit hyperactivity disorder, "attention" has now joined "memory" as a target area, and specific drugs, tailored to each, are being investigated. Some are available on the market. Beyond prescribing such drugs to treat identified disorders, it is relatively common for physicians to prescribe certain drugs "off-label." For example, Provigil, developed as a treatment for narcolepsy, is being used by some cellists, judges, airline pilots, and scientists to enhance attention and memory. Given the current public outrage over elite athletes' use of performance-enhancing drugs, it does not take much of a leap to consider the potential abuse of cognitive enhancement in competitive academic situations. Will there come a time when every student taking a college entrance exam will be required to pass a drug test, or when Nobel laureates, upon accepting the prize, will need to pledge that they were not aided in their work by cognitive enhancing agents?

In his day, Krech was somewhat of a lone wolf in his efforts to point out the social and ethical consequences of discoveries of neuroscience. Now, there is much greater public and professional awareness, and concerns have become more institutionalized. The new specialty of neuroethics has emerged, with centers at the University of Pennsylvania, Stanford and Oxford. An International Neuroethics Society has been founded, journals have been established, and conferences are held each year.

What is clear is that the dialogue among these new activists is a direct descendant of Krech's earlier call for action as he speculated on the social consequences of the explosion of research in brain, biochemistry and behavior.

Barbara Lusk is a professor of psychology at Collin College in Plano, Texas. Her work centers on the history of brain, biochemistry and behavior research — with a particular fondness for David Krech.

Katharine Milar, PhD, of Earlham College, is historical editor for "Time Capsule."